Project Summary/ Abstract Mosquitoes are important vectors for widespread human diseases from malaria to dengue, zika virus and chikungunya, and temperature and moisture detection are critical for supporting mosquito survival, reproduction and host-seeking. Accurately sensing environmental temperature is important for maintaining optimal body temperature, while sensing humidity is important for avoiding desiccation. Temperature and humidity are also important cues for host-seeking and blood-feeding, and moisture is important for oviposition as mosquito larvae are aquatic. But despite their importance, the molecular mechanisms underlying thermo- and hygro-sensing in mosquitoes remain largely unknown. Recent work in the Garrity lab has identified key members of a receptor family that modulate cold sensing and moisture sensing in the fruit fly Drosophila melanogaster. These receptors are conserved in vector mosquitoes and highly expressed in their antennae, consistent with the notion that they serve similar sensory roles. Anopheles gambiae is the major vector for malaria and was responsible for over two hundred million infections in 2015. Understanding the molecular mechanisms underlying temperature and humidity sensing in Anopheles gambiae could provide key insights for strategies to control this important disease vector and has potential implications for similar mechanisms in other vector mosquitoes. In my preliminary studies, I have used CRISPR/Cas9 genome editing in Anopheles gambiae to create mutants containing putative loss-of-function mutations in these receptors. I propose to use a combination of electrophysiology, immunohistochemistry and behavioral studies to establish the role(s) of these receptors in thermo- and hygro-sensing in the mosquito Anopheles gambiae. My work will address the sensory function of these receptors in mosquitoes and probe their potential roles in host-seeking behavior.